1. The issue was specific to PDF's only
2. No workflow. I was trying to open ANY PDF in ANY document library in SharePoint
3. A Web Application in SharePoint is a basically a new Sharepoint Website (in IIS) with a new URL, new content database, etc. You can have many web apps on a SharePoint server. No special setup, just bare bones since we were using it for testing, however, please note it was a test web application on our production server so it had all applicable services running.
Just for kicks, I created another web application, threw a PDF in a document library and wouldn't ya know it, I got the error again. I can copy the URL (getting it from properties in SP) and paste it into the browser and it opens fine. I can 'Download a Copy' from the SP menu and it opens fine. I will keep this web application intact to help troubleshoot this issue. Fortunately for me, my live web application - which all my users use - doesn't have this issue.